DESCRIPTION (Principal Investigator's Abstract): Serum cobalamin (vitamin B12) levels decrease with age, and low levels are frequent in the elderly. This is generally viewed as "normal" because most of them lack any classical evidence of cobalamin deficiency. However, it now seems likely that many, perhaps most, such "normal" low levels represent subtle cobalamin deficiency. The hallmark of the latter is unequivocal metabolic and/or electrophysiolgic evidence of deficiency (especially deosyuridine suppression abnormalities in marrow cells and evoked potential abnormalities) despite minimal clinical disturbance. Moreover, the case often seems to be malabsorption confined to food-bound cobalamin, rather than the classical but less common malabsorption of free cobalamin. Therefore, a large cohort of 3000 free-living elderly people will be tested. Those with low cobalamin levels will undergo study for subtle as well as classical cobalamin deficiency. Testing will focus on the highly sensitive deoxyuridine suppression test with and without in vitro vitamin additives, and visual and somatosensory evoked potentials. In addition to standard tests like blood counts and careful neurologic evaluation, we will also measure transcobalamins, folate, homocysteine and cobalamin analogue levels. Standard absorption testing will be combined with the egg yolk-cobalamin absorption test. Gastric status will be assessed because gastritis is common in the elderly and appears to be associated with food-cobalamin malabsorption. Blood tests of gastric status (especially pepsinogen I and pepsinogen II, but also including gastrin levels and antibodies to Helicobacter pylori, parietal cell and intrinsic factor) will be combined with gastric analysis (acid, pepsin and intrinsic factor content) and, in selected cases, gastric histology to establish the connection between gastric function and food-cobalamin malabsorption. A new in vitro test of gastric transfer of cobalamin from food to R binder will also be compared with these. Finally, we will monitor the response of subjects to treatment. Since low cobalamin levels are common in the aged and, if the hypothesis is correct, usually represent subtle cobalamin deficiency, such deficiency may be a common cause of mild dysfunction in a large proportion of the elderly population in the United States.